Mouse and rat putative premalignant hepatocellular lesions are to be studied by a variety of histochemical technics in order to learn whether or not oncogenesis proceeds in a sequential fashion. Enzymatic markers to be studied include ATPase, gamma glutamyltranspeptidase, glucose-6-phosphatase and alkaline phosphatase. Histochemical data will be combined with 3H-thymidine labelling indices in order to characterize phenotypically different populations of cells. In addition, the in vivo and in vitro regulation of cholesterol and bile acid synthesis as reflected by activities of HMG CoA reductase and cholesterol 7 alpha-hydroxylase will be studied in fully developed hepatomas and preneoplastic lesions.